CHARACTERIZATION OF THE ROLES OF SPHINGOSINE-1-PHOSPHATE IN ERYTHROCYTES

Abstract

Sphingosine-1-phosphate (S1P) is a powerful lipid mediator that activates 5 different G protein-coupled receptors. Recently, Mfsd2b was identified as a S1P transporter in the hematopoietic system. Sources of sphingosine for S1P production and the transport mechanism of Mfsd2b in erythrocytes are unknown. Our results highlight that erythrocytes are efficient in sphingosine uptake for S1P production and the release of S1P is dependent on Mfsd2b functions. We show that global deletion of Mfsd2b and Spns2 resulted in embryonic death between E13.5 and E14.5. Increased angiogenesis accompanied the haemorrhagic phenotypes in global DKO embryos, demonstrating that S1P from both transporters is required for blood vessel integrity. Given that erythrocytes are the main source of S1P, and malaria is a well-established model for intra-erythrocytic parasite, we studied the effects of S1P signalling on plasmodial invasions and development. We investigated the consequences of Mfsd2b deletion on invasion of Plasmodium falciparum and rodent malaria species.